Article ID Journal Published Year Pages File Type
5985301 Journal of Clinical Lipidology 2016 13 Pages PDF
Abstract

•Evacetrapib 100-mg monotherapy-lowered Lp(a) concentrations by 32%.•Evacetrapib 100 mg with a statin-lowered Lp(a) concentrations by 31%.•Evacetrapib 100-mg monotherapy-lowered sLDL particle concentrations by 84%.•Evacetrapib 100 mg with a statin-lowered sLDL particle concentrations by 60%.•Statin monotherapy had no effect on Lp(a) and sLDL particle concentrations.

BackgroundPotent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk.ObjectivesTo evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients.MethodsVLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30 mg/d, 100 mg/d, or 500 mg/d) or in combination with statins (100 mg plus simvastatin 40 mg/d, atorvastatin 20 mg/d, or rosuvastatin 10 mg/d; Clinicaltrials.gov Identifier: NCT01105975).ResultsEvacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to −40% with evacetrapib 500 mg), total LDL particle (LDL-P) (up to −54%), and small LDL particle (sLDL) (up to −95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (−31%), LDL-P (−22%), and sLDL (−60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000 nmol/L) and sLDL (>600 nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size.ConclusionsEvacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.

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